Burden of illness of people with persistent symptoms of schizophrenia: A multinational cross-sectional study.

BACKGROUND: Few studies have examined the impact of persistent symptoms of schizophrenia, especially with respect to patient-reported outcomes (PROs), carer burden and health economic impact. AIMS: Analyse data relating to burden and severity of illness, functional impairment and quality of life for patients with persistent symptoms of schizophrenia. METHODS: A cohort of stable outpatients with persistent symptoms of schizophrenia across seven countries were assessed in a multicentre, non-interventional, cross-sectional survey and retrospective medical record review using PRO questionnaires, clinical rating scales and carer questionnaires. RESULTS: Overall, 1,421 patients and 687 carers were enrolled. Approximately two-thirds of patients had moderate/mild schizophrenia with more severe negative symptoms predominating. Patients showed impaired personal/social functioning and unsuitability for work correlated with various patient factors, most notably symptom-related assessments. Quality-of-life assessments showed 25% to ⩾30% of patients had problems with mobility, washing or dressing. Carer burden was also considerable, with carers having to devote an average of 20.5 hours per week and notable negative impact on quality-of-life measures. Healthcare resource utilisation for in-hospital, outpatient and other care provider visits was significant. CONCLUSION: These results demonstrate the significant burden of schizophrenia for patients, carers and society and highlight the need for improved treatment approaches.

Health-related quality of life in patients with prominent negative symptoms: results from a multicenter randomized Phase II trial on bitopertin.

PURPOSE: Symptoms of schizophrenia fall into three categories (positive, negative and cognitive symptoms), which probably impact differently on patient's health-related quality of life (HRQoL). The present study aimed to explore HRQoL in patients with prominent negative symptoms. METHODS: In the 323 patients with prominent negative symptoms included in a multicenter Phase II trial investigating the safety and efficacy of bitopertin, HRQoL was assessed using the Schizophrenia Quality of Life Scale (SQLS), symptoms severity using the Positive and Negative Syndrome Scale and functioning using the Personal and Social Performance Scale. SQLS measurement properties were assessed; HRQoL was compared between treatment arms, and relationships between HRQoL, symptoms and functioning at baseline were explored. RESULTS: Both SQLS scores (Vitality/Cognition and Psychosocial Feelings) demonstrated good test-retest (ICC = 0.77 and 0.74) and internal consistency reliability (Cronbach's α = 0.86 and 0.93). Clinical validity with regard to schizophrenia severity and ability to detect change in severity of symptoms of schizophrenia were satisfactory. The SQLS structure was not formally disconfirmed. No statistically significant difference was observed between treatment arms. Negative symptoms were more strongly associated with functioning than positive symptoms. Functioning and Anxiety/Depression were strongly related to both SQLS domains. CONCLUSION: Overall, SQLS measurement properties were supported in these patients with prominent negative symptoms of schizophrenia. The impact of negative symptoms on functioning and HRQoL suggests that improving these symptoms will be a meaningful benefit in this population of patients.

Assessing the Impact of Caring for a Person with Schizophrenia: Development of the Schizophrenia Caregiver Questionnaire.

BACKGROUND: The responsibilities of caring for a person with schizophrenia may significantly impact informal caregivers' lives. The Zarit Burden Interview (ZBI) was originally developed to assess burden among caregivers of people with Alzheimer's disease. OBJECTIVE: This research was conducted to inform the development of a revised version of the ZBI, relevant to caregivers of people with schizophrenia. METHODS: Based on published qualitative research, the questionnaire was reviewed and modified in accordance with industry-standard guidelines. The resulting questionnaire [the Schizophrenia Caregiver Questionnaire (SCQ)] was then completed by 19 caregivers during cognitive debriefing interviews to assess understanding, relevance and comprehensiveness. RESULTS: Review of the ZBI resulted in a number of operational changes to improve face validity and potential sensitivity. Further questions were added based on key concepts identified in existing literature and minor phrasing alterations were made to improve content validity. Findings from caregiver interviews supported the content validity of the SCQ. CONCLUSION: The SCQ provides a comprehensive view of caregivers' subjective experiences of caregiving and demonstrated strong face and content validity. The questionnaire will be important in both clinical assessment and evaluating the efficacy of interventions designed to reduce or alleviate caregiver burden. Future research will seek to establish the psychometric validity of the questionnaire.

Defining therapeutic benefit for people with schizophrenia: focus on negative symptoms.

Schizophrenia is a complex, heterogeneous, multidimensional disorder within which negative symptoms are a significant and disabling feature. Whilst there is no established treatment for these symptoms, some pharmacological and psychosocial interventions have shown promise and this is an active area of research. Despite the effort to identify effective interventions, as yet there is no broadly accepted definition of therapeutic success. This article reviews concepts of clinical relevance and reports on a consensus conference whose goal was to apply these concepts to the treatment of negative symptoms. A number of key issues were identified and discussed including: assessment of specific negative symptom domains; defining response and remission for negative symptoms; assessment of functional outcomes; measurement of outcomes within clinical trials; and the assessment of duration/persistence of a response. The group reached a definition of therapeutic success using an achieved threshold of function that persisted over time. Recommendations were agreed upon with respect to: assessment of negative symptom domains of apathy-avolition and deficit of expression symptoms; thresholds for response and remission of negative symptoms based on level of symptomatology; assessing multiple domains of function including social occupation, activities of daily living, and socialization; the need for clinical trial data to include rate of change over time and converging sources of evidence; use of clinician, patient and caregiver perspectives to assess success; and the need for establishing criteria for the persistence of therapeutic benefit. A consensus statement and associated research criteria are offered as an initial step towards developing broad agreement regarding outcomes of negative symptoms treatment.

"Sometimes It's Difficult to Have a Normal Life": Results from a Qualitative Study Exploring Caregiver Burden in Schizophrenia.

Objectives. As a disease typified by early onset and chronic disease course, caring for a person with schizophrenia may have a significant impact on caregivers' lives. This study aimed to investigate the subjective experiences of caregivers of people with schizophrenia as a means of understanding "caregiver burden" in this population. Methods. Face-to-face qualitative interviews were conducted with a diverse sample of 19 US-English speaking caregivers of people with schizophrenia (who were at least moderately ill). Interview transcripts were analyzed using grounded theory methods and findings used to inform the development of a preliminary conceptual model outlining caregivers' experiences. Results. Findings support assertions that people with schizophrenia were largely dependent upon caregivers for the provision of care and caregivers subsequently reported lacking time for themselves and their other responsibilities (e.g., family and work). Caregiver burden frequently manifested as detriments in physical (e.g., fatigue, sickness) and emotional well-being (e.g., depression and anxiety). Conclusions. Caring for a person with schizophrenia has a significant impact on the lives of informal (unpaid) caregivers and alleviating caregiver burden is critical for managing individual and societal costs. Future research should concentrate on establishing reliable and valid means of assessing burden among caregivers of persons with schizophrenia to inform the development and evaluation of interventions for reducing this burden.

Relationship between modeling technique and reported outcomes: case studies in models for the treatment of schizophrenia.

Complex modeling techniques such as discrete-event simulation and simpler Markov or decision-tree models have been used to estimate the cost-effectiveness of treatment for chronic diseases such as schizophrenia. A systematic literature review of MEDLINE, EconLit, Embase, and the Cochrane Library identified schizophrenia modeling studies presenting incremental cost-effectiveness ratios. The relationship between modeling technique used and reported outcomes was examined. Fifty-four studies reporting results of 69 pairs of drug comparisons were identified. Of the paired-drug comparisons, 27 were conducted in at least two studies; in 14 of the 27, the results agreed (i.e., drug A cost-effective compared with drug B) despite differences in modeling techniques. Thirteen of the 27 paired-drug comparisons had contradictory study results even when the same modeling technique was used. Different modeling techniques did not appear to explain different findings about cost-effectiveness.

Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis.

BACKGROUND: There is an increased interest in evaluating the impact of core symptoms of schizophrenia, both positive and negative, on functioning and burden of disease. OBJECTIVE: To examine the extent to which prominent positive and prominent negative symptoms impact functional health, well-being, health-related quality of life (HRQoL), and family burden. METHODS: Data on symptomatology, HRQoL, and resource use from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) were analyzed (n=1447). Patients were divided into four groups based on the Positive and Negative Syndrome Scale (PANSS) using published criteria as having (a) neither prominent positive nor prominent negative symptoms (n=575; 39.7%); (b) only prominent negative symptoms (n=274; 18.9%); (c) only prominent positive symptoms (n=295; 20.4%); or (d) both prominent positive and negative symptoms (n=303; 20.9%). Differences were examined for overall significance between the groups and for a linear trend. RESULTS: There was a significant linear decline in the outcome measures with each subsequent symptom group, with the combination of prominent positive and negative symptoms incrementing the decline further on quality-adjusted life-years derived from the PANSS, Short-Form-12, Index of Functioning, HRQoL measures, and number of workdays missed by caregiver during the month prior to CATIE (all p<0.001). CONCLUSIONS: Both prominent positive and prominent negative symptoms of schizophrenia are independently associated with significant decline in functionality, HRQoL, and caregiver lost workdays. An increased burden is observed in patients with highest symptomatology. Further research is needed to determine predictors of poor outcomes and burden of schizophrenia.

Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data.

Increased attention has been given to treatment of negative symptoms and its potential impact on functional outcomes, however previous inferences have been confounded by the fact that measures of functional outcomes often use items similar to those of negative symptoms. We attempted to discern the relative effects of negative symptoms on functioning, as compared to other symptoms, using data from the National Institute of Mental Health CATIE trial of chronic schizophrenia (n=1447) by examining correlations of Positive and Negative Syndrome Scale factors, Calgary Depression Rating Scale and select items from Heinrich's and Lehman's Quality of Life Scales measuring aspects of functioning that did not overlap with negative symptoms. Baseline functioning and change in functioning were more strongly related to PANSS negative factor than any of the other symptoms - though the amount of variance explained by symptom changes in general was small. The data suggests that improvement in negative symptoms may have a distinctive and independent effect on functional outcome relative to other symptoms. This should be further tested in studies where negative symptoms improve without concomitant improvement of other symptoms.